Membrane potential, i.e., the electrical potential difference across the membrane of a living cell, is an intrinsic character of the live cell. Many important physiological processes, such as neuronal signaling, muscle contraction, cardiovascular function and immune response, involve a change in membrane potential. Generally, membrane potentials in cells depend on, inter alia, three factors: 1) the concentration of ions on the inside and outside of the cell; 2) the permeability of the cell membrane to those ions through specific ion channels; and 3) by the activity of electrogenic pumps that maintain the ion concentrations across the membrane. Therefore, ion channels that can selectively mediate the transfer of ions across the membrane of a cell may play a crucial role in establishing and controlling the membrane potential of the cell.
While ion channels may control the membrane potential of a cell, the membrane potential, however in a reverse way, can regulate the functions of many ion channels, especially voltage-dependent ion channels. For example, a change in membrane potential caused by the opening of a certain ion channel may affect behaviors of other ion channels and induce an action cascade of them, e.g., the contraction of muscle cells. In fact, abnormal membrane potential responses have been implicated in many severe human diseases such as hypertension, autosomal-dominant long-QT syndrome with deafness, autosomal-reccessive long-QT syndrome, benign familial neonatal convulsions, Long-QT syndrome, Long-QT syndrome with dysmorphic features, generalised epilepsy with febrile seizures (GEFS+), generalised epilepsy with febrile and afebrile seizures, paramyotonia congenita, potassium-aggravated myotonia hyperkalaemic periodic paralysis or Brugada syndrome.
While most studies have focused on natural ion channels, it is desirable to create synthetic ion channel systems that mimic biological functions of natural ion channels for controlling membrane potential and/or regulating natural voltage-dependent ion channels. To date, however, there is still no synthetic ion channel reported to be capable to set the membrane potentials and/or regulate natural voltage-dependent ion channels in living systems. Therefore, there is a need for new synthetic ion channels that can modulate membrane potential and/or regulate natural voltage-dependent ion channels and their physiological functions in living cells and tissues. Further, there is a need for methods of treating or preventing conditions and diseases that is related to the abnormal membrane potential responses.